Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study

Manuel Weber; Wolfgang P Fendler; Aravind S Ravi Kumar; Jeremie Calais; Johannes Czernin; Harun Ilhan; Fred Saad; Alexander Kretschmer; Turkay Hekimsoy; Sabine D Brookman-May; Suneel D Mundle; Eric J Small; Matthew R Smith; Paola M Perez; Thomas A Hope; Ken Herrmann; Michael S Hofman; Matthias Eiber; Boris A Hadaschik

doi:10.1016/j.eururo.2024.01.019

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study

Eur Urol. 2024 Mar 14:S0302-2838(24)00054-X. doi: 10.1016/j.eururo.2024.01.019. Online ahead of print.

Authors

Manuel Weber¹, Wolfgang P Fendler², Aravind S Ravi Kumar³, Jeremie Calais⁴, Johannes Czernin⁴, Harun Ilhan⁵, Fred Saad⁶, Alexander Kretschmer⁷, Turkay Hekimsoy⁸, Sabine D Brookman-May⁷, Suneel D Mundle⁹, Eric J Small¹⁰, Matthew R Smith¹¹, Paola M Perez¹⁰, Thomas A Hope¹⁰, Ken Herrmann¹, Michael S Hofman³, Matthias Eiber⁸, Boris A Hadaschik¹²

Affiliations

¹ Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.
² Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany. Electronic address: wolfgang.fendler@uk-essen.de.
³ Molecular Imaging and Therapeutic Nuclear Medicine, Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
⁴ University of California Los Angeles, Los Angeles, CA, USA.
⁵ Department of Nuclear Medicine, Ludwig-Maximilians-University, Munich, Germany.
⁶ Department of Surgery, Université de Montréal, Montréal, QC, Canada.
⁷ Department of Urology, Ludwig-Maximilians-University, Munich, Germany; Janssen Research & Development, Spring House, PA, USA.
⁸ Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
⁹ Janssen Research & Development, Raritan, NJ, USA.
¹⁰ Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
¹¹ Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA.
¹² Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany.

PMID: 38490855
DOI: 10.1016/j.eururo.2024.01.019

Abstract

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00-3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10-2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12-3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. PATIENT SUMMARY: A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment.

Keywords: Nonmetastatic castration-resistant prostate cancer; Prostate cancer; Prostate-specific membrane antigen positron emission tomography; SPARTAN.